Archaeal transcription shares close homology with eukaryotic Pol II transcription but involves many fewer molecular components. Archaeal transcription systems therefore offer much simpler model approaches to probing the mechanics of Pol II transcription and investigating the aberrant transcription often associated with genetic diseases and cancers. Euryarchaea also contain archaeal histones that package their DMA into archaeal nucleosomes which have the same basic structure, DMA wrapping and compaction properties as the (H3/H4)2 histone tetramer at the center of the eukaryotic nucleosome. Archaeal transcription systems can therefore also directly address regulation imposed by histones and chromatin. To date, only archaeal transcription initiation has been studied in detail. Very little is known about archaeal transcription elongation, and archaeal transcription termination has not been established in vitro. The experiments proposed will establish an archaeal in vitro transcription system that exhibits transcription termination, and will identify the molecular signals/proteins that direct termination in Archaea. I will also determine how an archaeal RNA polymerase transcribes through an archaeal nucleosome template and determine the fate of the nucleosome.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM073336-03
Application #
7234417
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Haynes, Susan R
Project Start
2005-07-01
Project End
2008-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$52,048
Indirect Cost
Name
Ohio State University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Pan, Miao; Santangelo, Thomas J; ?ubo?ová, Lubomíra et al. (2013) Thermococcus kodakarensis has two functional PCNA homologs but only one is required for viability. Extremophiles 17:453-61
Pan, Miao; Santangelo, Thomas J; Li, Zhuo et al. (2011) Thermococcus kodakarensis encodes three MCM homologs but only one is essential. Nucleic Acids Res 39:9671-80
Santangelo, Thomas J; Artsimovitch, Irina (2011) Termination and antitermination: RNA polymerase runs a stop sign. Nat Rev Microbiol 9:319-29
Li, Zhuo; Pan, Miao; Santangelo, Thomas J et al. (2011) A novel DNA nuclease is stimulated by association with the GINS complex. Nucleic Acids Res 39:6114-23
Santangelo, Thomas J; Cubonova, L'ubomira; Reeve, John N (2011) Deletion of alternative pathways for reductant recycling in Thermococcus kodakarensis increases hydrogen production. Mol Microbiol 81:897-911
Santangelo, Thomas J; Reeve, John N (2010) Deletion of switch 3 results in an archaeal RNA polymerase that is defective in transcript elongation. J Biol Chem 285:23908-15
Li, Zhuo; Santangelo, Thomas J; Cubonova, L'ubomira et al. (2010) Affinity purification of an archaeal DNA replication protein network. MBio 1:
Santangelo, Thomas J; Cubonova, L'ubomira; Reeve, John N (2010) Thermococcus kodakarensis genetics: TK1827-encoded beta-glycosidase, new positive-selection protocol, and targeted and repetitive deletion technology. Appl Environ Microbiol 76:1044-52
Santangelo, Thomas J; Cubonová, L'ubomíra; Skinner, Katherine M et al. (2009) Archaeal intrinsic transcription termination in vivo. J Bacteriol 191:7102-8
Hirata, Akira; Kanai, Tamotsu; Santangelo, Thomas J et al. (2008) Archaeal RNA polymerase subunits E and F are not required for transcription in vitro, but a Thermococcus kodakarensis mutant lacking subunit F is temperature-sensitive. Mol Microbiol 70:623-33

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